We propose to develop new reagents for photoaffinity labeling, and to use these reagents to discover receptor sites on membranes, and to specify active sites on enzymes. In particular, we wish to use 2-diazo-3,3,3-trifluoropropionates and other diazo reagents originating in these laboratories to label phenothiazine drugs that compete with dopamine for the dopamine receptor sites in guinea-pig brain. (The biological aspects of the work will be carried on in collaboration with Dr. Harold Klawans at the Michael Reese Hospital in Chicago.) If these reagents bind tightly, they may be covalently attached on photolysis, and permit the identification of the receptor. In another study, we recently synthesized disodium diazobenzylphosphonate; we would like to develop related but improved reagents with which to seek the active site of phosphatases. We also propose to investigate the mechanism of the enzymic decarboxylation of orotidylic acid. To this end, we are preparing an affinity column that utilizes inhibitors, based on ribosylbarituric acid-5'-phosphate, that have recently been synthesized in our laboratory.